Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0233794 (memory impairment)
 7,237 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pyramidal CA1 neurons of the hippocampus are critically involved in spatial learning and memory. These neurons are especially vulnerable to cerebral ischemia, but in spite of this, it has been consistently difficult to show any learning and memory deficits in two-vessel occlusion models of global ischemia. Transient global ischemia was induced in adult male rats under general anaesthesia administered by artificial respiration to prevent respiratory arrest. Systemic blood pressure was reduced to below 50 mmHg by instant adjustments of the halothane concentration, before and during bilateral occlusion of the carotid arteries. Cerebral blood flow was monitored by laser-Doppler flowmetry. Dying neurons were detected by TUNEL at 14 days after ischemia and surviving neurons by NeuN at 14 and 125 days after ischemia. Learning and memory was assessed in a novel water maze with three successive left-right choices. Transient global ischemia produced a profound and selective degeneration of CA1 neurons at 14 days after ischemia. This degeneration was associated with severe impairments in learning at 13 days after ischemia and in memory, as tested 24 h afterwards. At 125 days after ischemia, there was no significant learning and memory impairment, whereas the number of CA1 neurons was increased. These results show that transient global ischemia induced by two-vessel occlusion may lead to severe, but transient, impairments in learning and memory using a novel water maze, and that restored learning and memory is associated with an increased number of CA1 neurons.
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PMID:Profound but transient deficits in learning and memory after global ischemia using a novel water maze test. 1615 75

Recently, a potential neuroprotective effect of rimonabant, independent of the CB1 receptor interaction, has been proposed. In the present study, the role of transient receptor potential channel vanilloid subfamily member 1, named VR1, on neuroprotective effect of rimonabant, on global cerebral ischemia in gerbils, was investigated. Rimonabant (0.05-3 mg kg-1), given i.p. 5 min after recirculation, dose dependently antagonized the ischemia-induced decrease in electroencephalographic (EEG) total spectral power and restored relative frequency band distribution 7 days after ischemia. Rimonabant (0.125-0.5 mg kg-1) fully prevented ischemia-induced hyperlocomotion 1 day after ischemia and memory impairment evaluated in a passive avoidance task, 3 days after ischemia. At 7 days after ischemia, the survival of pyramidal cells, in the CA1 subfield, was respectively 91 and 96%, in the animals given rimonabant 0.25 and 0.5 mg kg-1, compared to the vehicle group. Higher doses were not protective. The protection induced by rimonabant followed a bell-shaped curve, the maximal active doses being 0.25 and 0.5 mg kg-1. Capsazepine (0.01 mg kg-1), a selective VR1 vanilloid receptor antagonist, completely reversed rimonabant-induced neuroprotective effects against EEG flattening, memory impairment and CA1 hippocampal neuronal loss. These findings suggest that VR1 vanilloid receptors are involved in rimonabant's neuroprotection even if other mechanisms can contribute to this effect.
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PMID:Vanilloid VR1 receptor is involved in rimonabant-induced neuroprotection. 1644 89

Excitotoxicity is thought to be a major mechanism in many human disease states such as ischemia, trauma, epilepsy and chronic neurodegenerative disorders. Briefly, synaptic overactivity leads to the excessive release of glutamate that activates postsynaptic cell membrane receptors, which upon activation open their associated ion channel pore to produce ion influx. To date, although molecular basis of glutamate toxicity remain uncertain, there is general agreement that N-methyl-d-aspartate (NMDA) subtype of ionotropic glutamate receptors plays a key role in mediating at least some aspects of glutamate neurotoxicity. On this view, research has focused in the discovery of new compounds able to either reduce glutamate release or activation of postsynaptic NMDA receptors. Although NMDA receptor antagonists prevent excitotoxicity in cellular and animal models, these drugs have limited usefulness clinically. Side effects such as psychosis, nausea, vomiting, memory impairment, and neuronal cell death accompany complete NMDA receptor blockade, dramatizing the crucial role of the NMDA receptor in normal neuronal processes. Recently, however, well-tolerated compounds such as memantine has been shown to be able to block excitotoxic cell death in a clinically tolerated manner. Understanding the biochemical properties of the multitude of NMDA receptor subtypes offers the possibility of developing more effective and clinically useful drugs. The increasing knowledge of the structure and function of this postsynaptic NMDA complex may improve the identification of specific molecular targets whose pharmacological or genetic manipulation might lead to innovative therapies for brain disorders.
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PMID:New targets for pharmacological intervention in the glutamatergic synapse. 1683 14

Peroxynitrite involvement has been implicated in the neuronal damage. In the present study, we have investigated the neuroprotective effects of peroxynitrite decomposition catalyst (FeTMPyP) on global cerebral ischemia. Global cerebral ischemia-reperfusion (IR) injury was produced by 5 min occlusion of both common carotid arteries followed by reperfusion of 96 h in the adult male Mongolian gerbils. The extent of injury was assessed behaviorally by measuring neurological functions, locomotor activity, passive avoidance test and by histopathological evaluation of extent of damage to CA1 hippocampal pyramidal region. FeTMPyP (1 and 3 mgkg(-1), i.p., administered 30 min prior to ischemia) treatment improved the neurological functions, reduced the hyperlocomotion and memory impairment in IR challenged gerbils. The loss of neurons from the pyramidal layer of the CA1 region caused by global IR injury was attenuated with FeTMPyP. FeTMPyP also inhibited lipid peroxidation as evident from reduction in brain malondialdehyde levels. These results suggest that peroxynitrite decomposition catalyst may be effective neuroprotective agent for global cerebral ischemia.
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PMID:Neuroprotective effects of FeTMPyP: a peroxynitrite decomposition catalyst in global cerebral ischemia model in gerbils. 1687 4

Only two cases connecting Sildenafil reception and acute memory impairment have been published. Two similar cases were observed in our clinic last year. Sildenafil is a potent inhibitor of cyclic guanosine monophosphate in the corpus cavernosum and therefore, increases the penile response to sexual stimulation and is used for erectile dysfunction. The most severe and life-threatening complications of Sildenafil are associated with combined administration with nitrates. The incidence of nonfatal myocardial infarction, stroke and death did not significantly differ between Sildenafil-treated and placebo-treated patients; therefore, Sildenafil does not appear contraindicated in subjects with ischemic heart disease (IHD). Scanty data are available regarding Sildenafil and cerebrovascular disease and there are only a few case reports regarding transient global amnesia (TGA) after Sildenafil use. Two cases of TGA are described immediately following the use of one dose of Sildenafil. The etiology of TGA is not yet completely understood but one of the hypothesizes suggests that the pathophysiology of this condition is related to intracranial vasomotor changes, especially due to venous congestion and venous ischemia of bilateral hippocampal structures. It is also well known that Sildenafil stimulates the relaxation of smooth muscle and causes vasomotor changes. Based on this report, as well as previous reports, it is suggested that a single dose of Sildenafil may stimulate TGA.
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PMID:[Two cases of transient global amnesia (TGA) following sildenafil use]. 1707 26

Spatial cognitive impairment is common after stroke insults. Voluntary exercise could improve the impaired spatial memory. Newly generated neurons in the dentate gyrus are necessary for the acquisition of new hippocampus-dependent memories. However, it is not well known whether voluntary exercise after stroke promotes neurogenesis in the adult dentate gyrus, thereby promoting spatial memory recovery. Here, we examined in mice subjected to focal cerebral ischemia the effect of voluntary or forced exercise on neurogenesis in the ischemic dentate gyrus and spatial memory. Exposure to voluntary wheel running after stroke enhanced newborn cell survival and up-regulated the phosphorylation of cAMP response element binding protein (CREB) in the dentate gyrus and reversed ischemia-induced spatial memory impairment. However, the enhanced newborn cell survival and CREB phosphorylation in the dentate gyrus and improved spatial memory were not observed in the mice exposed to forced swimming. Moreover, there was a significant correlation between the total number of surviving newborn cells in the dentate gyrus and the ability of mice to locate the platform in the Morris water maze. These results suggest that, in the adult mice, exposure to voluntary exercise after ischemic stroke may promote newborn cells survival in the dentate gyrus by up-regulating CREB phosphorylation and consequently restore impaired hippocampus-dependent memory.
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PMID:Voluntary exercise-induced neurogenesis in the postischemic dentate gyrus is associated with spatial memory recovery from stroke. 1746 31

Lithium is a major drug used for the treatment of bipolar mood disorder and has recently been shown to have neuroprotective properties. In this study we investigated the neuroprotective effects of lithium in gerbils subjected to global cerebral ischemia, an animal model of stroke. The ischemia-induced exploratory behavior changes, measured by open field testing, were largely suppressed by lithium treatment for 7 days prior to ischemic onset. Similarly, memory impairments, measured by T-maze testing, were prevented by lithium pretreatment. This is believed to be the first report of lithium-induced protection against hyperactivity in a novel open field and memory impairment in a gerbil model of global ischemia. These behavioral benefits were associated with an increase in viable cells as measured by hematoxylin and eosin staining and a decrease in apoptotic TUNEL-positive cells in the CA1 hippocampal area of ischemic gerbils. Moreover, the lithium-induced neuroprotection was accompanied by down-regulation of pro-apoptotic p53 in the CA1 but up-regulation of anti-apoptotic Bcl-2 and heat shock protein 70 (HSP70) in the ischemic brain. These results underscore the ability of lithium to improve functional behavioral outcome in gerbil and rodent cerebral ischemic models and further indicate the potential therapeutic use of lithium in certain human stroke conditions.
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PMID:Lithium reduces ischemia-induced hippocampal CA1 damage and behavioral deficits in gerbils. 1802 86

The present study is aimed at evaluating the functional and neuroprotective effect of benzamide, a poly-(ADP-ribose) polymerase (PARP) inhibitor on delayed neuronal death (DND) in hippocampus CA1 region and memory impairment following global cerebral ischemia (GCI) in a mouse model. GCI was induced by bilateral common carotid artery occlusion (BCAo) for 20 min followed by reperfusion for 9 days. Postischemic continuous treatment with benzamide (160 mg/kg b w i.p. for 9 days) significantly reversed the GCI-induced anterograde memory impairment in passive avoidance step through and elevated plus maze tasks. The observed memory impairment in vehicle treated ischemia group was found to be well correlated with DND and downregulation of cholinergic muscarinic receptor-1 expression, which was possibly mediated by inflammation and apoptosis, as revealed from inducible nitric oxide synthase (iNOS) expression and number of TUNEL positive neurons in hippocampus CA1 region. It is clear from the present experiment that benzamide treatment significantly decreases the iNOS expression and number of apoptotic neurons and thereby improves the neuronal survival and memory during GCI. Our present findings provide compelling evidence that multiple doses of benzamide treatment is a promising therapeutic approach for cerebrovascular and neurodegenerative diseases, which deserves further clinical evaluation.
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PMID:Benzamide protects delayed neuronal death and behavioural impairment in a mouse model of global cerebral ischemia. 1850 76

Our previous results indicated that stimulation by daily environmental enrichment (EE) recovered memory deficits without affecting hippocampus damage in adult male rats submitted to neonatal hypoxia-ischemia (HI). The present study investigated whether early continuous housing in an enriched environment would be effective in preventing spatial and recognition memory both in adolescent and adult female and male rats, as well as the possible benefits of continuous EE in alleviating hippocampal and striatal atrophy consequent to the neonatal HI. Wistar rats in the 7th PND were submitted to the HI and, in the day after, were housed in an enriched environment (8th-30th PND). Subsequently, performance of animals in the novel-object recognition and in two water maze tasks was assessed; in adulthood, animals' behavior was reassessed in the water maze. Rats were sacrificed and both hippocampal volume and striatal area were estimated following the completion of behavioral study. Post-HI cognitive deficits in the object recognition test were completely recovered by the EE. However, memory impairment in the water maze was only partially prevented by EE; this effect was observed especially in female rats on the working memory protocol. As for the morphological assessment, there was no enrichment effect over the loss of hippocampus volume and striatum area. In conclusion, present data indicate that early housing in EE caused performance recovery in object recognition and a partial improvement in the working memory spatial task in adolescent females after neonatal HI; however no effects of enrichment were revealed in adult animal's performance or in the extension of tissue atrophy of hippocampus and striatum consequent to HI.
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PMID:Early enriched housing results in partial recovery of memory deficits in female, but not in male, rats after neonatal hypoxia-ischemia. 1851 67

Cognitive deficits, including spatial memory impairment, are very common after ischemic stroke. Neurogenesis in the dentate gyrus (DG) contributes to forming spatial memory in the ischemic brain. Fluoxetine, a selective serotonin reuptake inhibitor, can enhance neurogenesis in the hippocampus in physiological situations and some neurological diseases. However, whether it has effects on ischemia-induced spatial cognitive impairment and hippocampal neurogenesis has not been determined. Here we report that fluoxetine treatment (10 mg kg(-1), i.p.) for 4 weeks promoted the survival of newborn cells in the ischemic hippocampus and, consequently, attenuated spatial memory impairment of mice after focal cerebral ischemia. Disrupting hippocampal neurogenesis blocked the beneficial effect of fluoxetine on ischemia-induced spatial cognitive impairment. These results suggest that chronic fluoxetine treatment benefits spatial cognitive function recovery following ischemic insult, and the improved cognitive function is associated with enhanced newborn cell survival in the hippocampus. Our results raise the possibility that fluoxetine can be used as a drug to treat poststroke spatial cognitive deficits.
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PMID:Chronic fluoxetine treatment improves ischemia-induced spatial cognitive deficits through increasing hippocampal neurogenesis after stroke. 1871 44


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